Restoring SRSF3 in Kupffer cells attenuates obesity-related insulin resistance.

ABSTRACT:

Background and aims

In obesity, depletion of KCs expressing CRIg (complement receptor of the Ig superfamily) leads to microbial DNA accumulation, which subsequently triggers tissue inflammation and insulin resistance. However, the mechanism underlying obesity-mediated changes in KC complement immune functions is largely unknown.

Approach and results

Using KC-specific deactivated Cas9 transgenic mice treated with guide RNA, we assessed the effects of restoring CRIg or the serine/arginine-rich splicing factor 3 (SRSF3) abundance on KC functions and metabolic phenotypes in obese mice. The impacts of weight loss on KC responses were evaluated in a diet switch mouse model. The role of SRSF3 in regulating KC functions was also evaluated using KC-specific SRSF3 knockout mice. Here,

SUBMITTER: Gao H 

PROVIDER: S-EPMC11254564 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature